OCB03-2008 ACETYLCHOLINE Flashcards

1
Q

How is acetylcholine formed?

A

Formed from choline by choline acetyl transferase

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2
Q

How is the action of ACh terminated?

A

ACh hydrolysed by acetylcholinesterase on the postsynaptic membrane

Choline transported back into presynaptic neuron

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3
Q

What reaction is catalysed by acetylcholinesterase?

A

ACh –> acetate + choline

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4
Q

What are the two types of ACh receptor?

A

Nicotinic

Muscarinic

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5
Q

Describe a nicotinic ACh receptor. (3)

A

Ion channel

Pre and postsynaptic

5 subunits - 2α and 3β

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6
Q

Where are the ACh binding sites on a nAChR?

A

α subunits (2 sites)

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7
Q

How many types of α subunits are there that can form part of a nAChR?

A

8

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8
Q

What is the effect of activating a presynaptic nAChR?

A

Neurotransmitter release due to Ca++ influx

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9
Q

What is the effect of activating a postsynaptic nAChR?

A

Depolarisation to mediate fast excitation

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10
Q

What happens when a nAChR is activated?

A

Conformational change = pore opens

Na+, K+ and Ca++ enter cell

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11
Q

How many ACh molecules are required to activate a nAChR?

A

2

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12
Q

What is the structure of a nAChR common in the CNS?

A

(α4)2(β2)3

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13
Q

What are the nAChR responsible for in the CNS?

A

Addiction

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14
Q

Describe a muscarinic ACh receptor.

A

GPCR

Pre and postsynaptic

Enhances or inhibits target neuron activity

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15
Q

How many types of mAChR are there?

A

5

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16
Q

What G proteins are the mAChRs coupled to?

A

1, 3, 5 = Gq

2, 4 = Gi

17
Q

What happens when the odd numbered mAChRs are activated?

A

Phospholipase C hydrolyses membrane-bound lipid (PIP2) to form IP3 and DAG

IP3 liberates Ca++ from intracellular stores

DAG activated protein kinase C to phosphorylate channels

18
Q

What is PIP2 and what does it do?

A

Phosphatidyl inositol bisphosphate

Binds K channels to regulate activity; hydrolysis of PIP2 closes K channels

19
Q

What does IP3 stand for?

A

Inositol triphosphate

20
Q

What does DAG stand for?

A

Diacylglycerol

21
Q

What happens when the even numbered mAChRs are activated?

A

Adenylyl cyclase inhibited

Close Ca channels or open K channels depending on location (inhibitory)

22
Q

Where are cholinergic pathways found in the brain?

A

Basal forebrain to cortex, amygdala, hippocampus

Brainstem

Striatum (caudate nucleus/putamen)

Retina

23
Q

What are the main responsibilities of the amygdala?

A

Memory

Decision-making

Emotions

24
Q

What are the main responsibilities of the hippocampus?

A

Learning

Memory

25
Q

How are cholinergic pathways implicated in Alzheimer’s disease?

A

Early reduction in basal forebrain fibres innervating the cortex

26
Q

What can be used to treat Alzheimer’s disease?

A

Anti-cholinesterase drugs (increase ACh)

27
Q

What type of drug is galantamine?

A

Anti-cholinesterase drug

28
Q

What is the role of ACh in the brainstem?

A

Musculoskeletal and parasympathetic motor pathways from cranial nerve nuclei

Reticular activating system with pontine nucleus for arousal and consciousness

29
Q

What is the role of ACh in the striatum (caudate nucleus/putamen)?

A

~1% are constantly active cholinergic interneurons which innervate the GABAergic medium spiny interneurons which output to the globus pallidus (proprioceptive movements)

30
Q

What is the role of ACh in the retina?

A

Interneurons (eg amacrine cells)

31
Q

How does ACh affect arousal/increased attention to sensory input?

A

Brainstem cholinergic neurons activate thalamic and cortical centres to increase arousal

32
Q

How does ACh affect consciousness and REM sleep?

A

Acts with GABAergic system

M1 and M3 thought to be important in pattern of REM sleep

33
Q

How does ACh affect motor control?

A

Regulates dopamine activity and release (mAChR)

34
Q

What drugs can be used to treat tremor in early Parkinson’s disease (ACh)?

A

Muscarinic antagonists

35
Q

How does ACh affect ingestive behaviour?

A

Interneurons and nucleus accumbens release ACh to influence food/other intake (may be involved in addiction)

36
Q

Which AChRs contribute to learning and memory?

A

Muscarinic receptors